Ticks are the most important arthropod vectors capable of transmitting a diverse array of pathogens to
humans. Several environmental and sociological factors have contributed to the range and population
expansion of ticks, resulting in an increased number of tick-borne diseases (TBDs) in the United States.
Recent tick surveillance studies have demonstrated that Amblyomma americanum (lone star tick) has rapidly
expanded northward and become the dominant tick species, displacing local tick species such as Ixodes
scapularis (deer tick) and Dermacentor variabilis (American dog tick) in the Northeast and Midwest, where the
increased number of patients with TBDs of unknown etiology has been observed. A. americanum poses a
public health threat as the tick presents non-discriminating aggressive biting behavior and serves as a vector
and reservoir for diverse human pathogens, including Rickettsia amblyommatis (rickettsiosis), Ehrlichia
chaffeensis and E. ewingii (human ehrlichiosis), Francisella tularensis (tularemia), Heartland virus (Heartland
virus disease), Bourbon virus (Bourbon virus disease), and Borrelia lonestari (Southern tick-associated rash
illnesses). R. amblyommatis, a Gram-negative pathogen that belongs to the spotted fever group of Rickettsia,
has been frequently identified from A. americanum in several parts of the United States. In contrast, the current
prevalence of R. rickettsii (Rocky Mountain spotted fever, RMSF) in D. variabilis is estimated to be less than
1%. The high prevalence of R. amblyommatis, combined with the aggressive biting behavior of A. americanum,
enhances the probability of human infections with R. amblyommatis. Within ticks, R. amblyommatis exhibits
obligatory intracellular lifecycle in multiple organ tissues such as ovaries, midgut, and salivary glands, enabling
R. amblyommatis transmission to offspring and mammalian hosts. Several lines of clinical and serological
evidence suggest that R. amblyommatis is the etiological agent of RMSF-like illness. Analysis of paired sera
from patients diagnosed with probable RMSF revealed that some patients developed antibodies to R.
amblyommatis, but not to R. rickettsii, corroborating that R. amblyommatis may cause RMSF-like illnesses in
humans. Those patients with specific reactivity to R. amblyommatis presented typical clinical manifestations of
a mild RMSF with fever, headache, and myalgia. However, there is a significant gap in our understanding of R.
amblyommatis biology and its virulence potential to cause rickettsiosis in mammalian hosts. Based on the
available evidence of 1) the invasion and expansion of A. americanum heavily infected with R. amblyommatis
in the upper Midwestern and the Northeastern United States; 2) the increasing numbers of RMSF-like cases in
the same areas; 3) experimental results from our laboratory for R. amblyommatis-induced cytopathology and
pathogenesis, we will investigate the genetic basis of R. amblyommatis from one of the northernmost hotspots
for this species, determine the virulence potential in tissue culture and animal infection models, and study the
host-pathogen-vector interactions enabling R. amblyommatis rickettsiosis.